The overall objectives of this project are to study the mechanisms by which carcinogens induce bladder cancer and to study factors which may intervene in these mechanisms to prevent such cancers. The interaction of N-(4-(5-nitro-2-furyl)-2-thiazolyl) formamide (FANFT), labeled by conjugation with an azo dye, with DNA and polynucleotides will be studied in vitro. The effects of allopurinol and 2,5-di-O-acetylglucosaccharo-(1 yields 4) (6 yields 3)-dilactone on the carcinogenicity of N-butyl-N-(4-hydroxybutyl) nitrosamine will be evaluated. The influence of these two compounds on tissue distribution and macromolecular binding of (14C) FANFT in rats will be determined. Rats will be fed uracil to produce urinary stones, and the effect of these stones on the induction of bladder cancer by FANFT will be ascertained. Harmane, an element of charred meat and a known comutagen, is thought to be a metabolite of tryptophan. Harmane's ability to promote bladder carcinogenesis will be studied. Two mutagenic hydroxamic acids, 2-naphthohydroxamic acids and benzoylaminoacethydroxamic acid, will be fed to rats to assess their carcinogenicity. Finally, a series of polyphenolic compounds will be tested for mutagenicity. These studies may have relevance to the prevention of human bladder cancers in that they will contribute to the understanding of bladder tumorigenesis in experimental animals and in the identification of environmental carcinogens.